PLD2

Summary

PLD2 (phospholipase D2, HGNC:9068) is a protein-coding gene on chromosome 17p13.2, encoding Phospholipase D2 (O14939). Function as phospholipase selective for phosphatidylcholine.

The protein encoded by this gene catalyzes the hydrolysis of phosphatidylcholine to phosphatidic acid and choline. The activity of the encoded enzyme is enhanced by phosphatidylinositol 4,5-bisphosphate and ADP-ribosylation factor-1. This protein localizes to the peripheral membrane and may be involved in cytoskeletal organization, cell cycle control, transcriptional regulation, and/or regulated secretion. Two transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 5338 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 187 total
• GTEx eGene: eQTL in 37 tissues, sQTL in 48 (q < 0.05)
• ChEMBL bioactivity: 2 clinical-phase molecules tested; no curated mechanism-of-action drug
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 0.93 (unconstrained)
• MANE Select transcript: NM_002663
• Notable: 187 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9068
Approved symbol	PLD2
Name	phospholipase D2
Location	17p13.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000129219
Ensembl biotype	protein_coding
OMIM	602384
Entrez	5338

Gene structure

Transcript identifiers

Ensembl transcripts: 38 — 15 protein_coding, 15 nonsense_mediated_decay, 8 retained_intron

MANE Select: ENST00000263088

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 2, TSL 2: 4, TSL 3: 4, TSL 4: 3, TSL 5: 2

ENST00000263088, ENST00000571273, ENST00000572127, ENST00000572199, ENST00000572940, ENST00000573258, ENST00000574268, ENST00000574796, ENST00000575246, ENST00000575316, ENST00000575813, ENST00000575945, ENST00000576329, ENST00000576864, ENST00000576983, ENST00000879130, ENST00000879131, ENST00000879132, ENST00000879133, ENST00000928900, ENST00000964340, ENST00000964341, ENST00001003408, ENST00001019231, ENST00001019232, ENST00001019233, ENST00001019234, ENST00001019235, ENST00001019236, ENST00001019237, ENST00001019238, ENST00001019239, ENST00001019240, ENST00001019241, ENST00001087968, ENST00001110583, ENST00001113134, ENST00001141019

RefSeq mRNA: 2 — MANE Select: NM_002663 NM_001243108, NM_002663

CCDS: CCDS11057, CCDS58507

Canonical transcript exons

ENST00000263088 — 25 exons

Exon	Start	End
ENSE00000676905	4821793	4821907
ENSE00000886994	4819429	4819582
ENSE00001126213	4818297	4818385
ENSE00001126221	4818002	4818106
ENSE00001126318	4808274	4808416
ENSE00001126323	4807984	4808114
ENSE00001360015	4807152	4807225
ENSE00002681387	4822640	4823430
ENSE00003475241	4816620	4816746
ENSE00003484430	4817146	4817259
ENSE00003508147	4810802	4810951
ENSE00003544480	4814633	4814711
ENSE00003545577	4809100	4809205
ENSE00003549859	4809877	4810029
ENSE00003555968	4809298	4809363
ENSE00003590900	4814418	4814501
ENSE00003592063	4816937	4817055
ENSE00003592812	4819084	4819218
ENSE00003603465	4809493	4809551
ENSE00003609127	4809691	4809783
ENSE00003611606	4818774	4818823
ENSE00003614118	4815764	4815934
ENSE00003638098	4815476	4815586
ENSE00003670738	4807772	4807881
ENSE00003676693	4818494	4818607

Expression profiles

Bgee: expression breadth ubiquitous, 274 present calls, max score 98.17.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 7.5855 / max 84.9924, expressed in 1735 samples.

Highest expression (Bgee): lower esophagus mucosa, esophagus mucosa, skin of leg, hemisphere of cerebellum, ectocervix.

Genetic regulation across tissues (GTEx eQTL / sQTL)

PLD2 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 37 tissues and its splicing (sQTL) in 48 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 85 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Skin Sun Exposed Lower leg	sqtl	1.4e-111	-1.35	17:4819581:G:A
Skin Not Sun Exposed Suprapubic	sqtl	2.8e-85	-1.32	17:4819581:G:A
Esophagus Mucosa	sqtl	8.3e-85	-1.43	17:4819581:G:A
Adipose Subcutaneous	sqtl	4.4e-76	-1.31	17:4819581:G:A
Nerve Tibial	sqtl	2.4e-61	-1.21	17:4819581:G:A
Thyroid	sqtl	3.8e-56	-1.18	17:4819581:G:A
Cells Cultured fibroblasts	eqtl	3.6e-55	-0.46	17:4807191:C:G
Lung	sqtl	2.1e-49	-1.23	17:4819581:G:A
Whole Blood	eqtl	1.4e-47	-0.62	17:4807191:C:G
Breast Mammary Tissue	sqtl	6.6e-44	-1.24	17:4819581:G:A
Artery Tibial	sqtl	2.9e-41	-1.09	17:4819581:G:A
Adipose Visceral Omentum	sqtl	3.9e-39	-1.19	17:4819581:G:A
Brain Cerebellar Hemisphere	sqtl	2.1e-33	-1.54	17:4819581:G:A
Artery Tibial	eqtl	5.3e-33	-0.38	17:4807191:C:G
Thyroid	eqtl	8.8e-31	+0.39	17:4802814:T:C
Whole Blood	sqtl	9.9e-30	-0.85	17:4819581:G:A
Esophagus Muscularis	sqtl	2.4e-29	-1.15	17:4819581:G:A
Artery Aorta	sqtl	7.8e-28	-1.19	17:4819581:G:A
Esophagus Gastroesophageal Junction	sqtl	1.6e-27	-1.23	17:4819581:G:A
Cells Cultured fibroblasts	sqtl	1.8e-27	-0.96	17:4819581:G:A

FANTOM5 promoters

1 alternative TSS:

Promoter ID	TPM avg	Samples expressed
158945	7.5855	1735

Top tissues by expression

showing 100 of 290 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
lower esophagus mucosa	UBERON:0035834	98.17	gold quality
esophagus mucosa	UBERON:0002469	96.67	gold quality
skin of leg	UBERON:0001511	95.09	gold quality
right hemisphere of cerebellum	UBERON:0014890	95.09	gold quality
ectocervix	UBERON:0012249	94.55	gold quality
right ovary	UBERON:0002118	94.54	gold quality
skin of abdomen	UBERON:0001416	94.53	gold quality
cerebellar hemisphere	UBERON:0002245	94.51	gold quality
cerebellar cortex	UBERON:0002129	94.33	gold quality
minor salivary gland	UBERON:0001830	94.09	gold quality
left ovary	UBERON:0002119	93.88	gold quality
tibial nerve	UBERON:0001323	93.38	gold quality
apex of heart	UBERON:0002098	93.20	gold quality
ventricular zone	UBERON:0003053	93.12	gold quality
mouth mucosa	UBERON:0003729	92.96	gold quality
esophagus	UBERON:0001043	92.88	gold quality
cerebellum	UBERON:0002037	92.74	gold quality
body of uterus	UBERON:0009853	92.64	gold quality
vagina	UBERON:0000996	92.59	gold quality
endocervix	UBERON:0000458	92.35	gold quality
zone of skin	UBERON:0000014	92.28	gold quality
pharyngeal mucosa	UBERON:0000355	92.25	gold quality
vena cava	UBERON:0004087	92.21	gold quality
saliva-secreting gland	UBERON:0001044	91.91	gold quality
right coronary artery	UBERON:0001625	91.69	gold quality
lateral globus pallidus	UBERON:0002476	91.61	gold quality
left uterine tube	UBERON:0001303	91.56	gold quality
right uterine tube	UBERON:0001302	91.40	gold quality
gall bladder	UBERON:0002110	91.11	gold quality
sural nerve	UBERON:0015488	90.94	gold quality
right lung	UBERON:0002167	90.82	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	90.82	gold quality
granulocyte	CL:0000094	90.76	gold quality
descending thoracic aorta	UBERON:0002345	90.57	gold quality
upper lobe of left lung	UBERON:0008952	90.33	gold quality
body of tongue	UBERON:0011876	90.24	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	90.18	gold quality
spinal cord	UBERON:0002240	90.12	gold quality
metanephros cortex	UBERON:0010533	90.12	gold quality
adenohypophysis	UBERON:0002196	90.08	gold quality
stromal cell of endometrium	CL:0002255	89.92	gold quality
omental fat pad	UBERON:0010414	89.92	gold quality
peritoneum	UBERON:0002358	89.91	gold quality
smooth muscle tissue	UBERON:0001135	89.82	gold quality
subcutaneous adipose tissue	UBERON:0002190	89.67	gold quality
ascending aorta	UBERON:0001496	89.60	gold quality
thoracic aorta	UBERON:0001515	89.60	gold quality
ovary	UBERON:0000992	89.43	gold quality
type B pancreatic cell	CL:0000169	89.42	silver quality
uterine cervix	UBERON:0000002	89.28	gold quality
ganglionic eminence	UBERON:0004023	89.26	gold quality
adipose tissue of abdominal region	UBERON:0007808	89.22	gold quality
muscle layer of sigmoid colon	UBERON:0035805	89.10	gold quality
right frontal lobe	UBERON:0002810	89.09	gold quality
spleen	UBERON:0002106	89.02	gold quality
right lobe of thyroid gland	UBERON:0001119	88.99	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	88.95	gold quality
putamen	UBERON:0001874	88.90	gold quality
coronary artery	UBERON:0001621	88.86	gold quality
tongue	UBERON:0001723	88.81	gold quality
body of stomach	UBERON:0001161	88.79	gold quality
body of pancreas	UBERON:0001150	88.78	gold quality
upper lobe of lung	UBERON:0008948	88.70	gold quality
left coronary artery	UBERON:0001626	88.68	gold quality
lower esophagus	UBERON:0013473	88.64	gold quality
left lobe of thyroid gland	UBERON:0001120	88.59	gold quality
fundus of stomach	UBERON:0001160	88.59	gold quality
caudate nucleus	UBERON:0001873	88.59	gold quality
lower esophagus muscularis layer	UBERON:0035833	88.59	gold quality
mucosa of stomach	UBERON:0001199	88.58	gold quality
small intestine Peyer’s patch	UBERON:0003454	88.57	gold quality
amygdala	UBERON:0001876	88.53	gold quality
substantia nigra	UBERON:0002038	88.53	gold quality
cardia of stomach	UBERON:0001162	88.40	gold quality
midbrain	UBERON:0001891	88.29	gold quality
pituitary gland	UBERON:0000007	88.21	gold quality
olfactory bulb	UBERON:0002264	88.20	silver quality
transverse colon	UBERON:0001157	88.18	gold quality
aorta	UBERON:0000947	88.15	gold quality
nasal cavity epithelium	UBERON:0005384	88.09	gold quality
subthalamic nucleus	UBERON:0001906	88.02	gold quality
nucleus accumbens	UBERON:0001882	87.96	gold quality
monocyte	CL:0000576	87.79	gold quality
stomach	UBERON:0000945	87.76	gold quality
triceps brachii	UBERON:0001509	87.72	gold quality
thyroid gland	UBERON:0002046	87.72	gold quality
lateral nuclear group of thalamus	UBERON:0002736	87.60	gold quality
mononuclear cell	CL:0000842	87.59	gold quality
pancreatic ductal cell	CL:0002079	87.55	silver quality
gluteal muscle	UBERON:0002000	87.45	gold quality
leukocyte	CL:0000738	87.36	gold quality
superior surface of tongue	UBERON:0007371	87.35	gold quality
saphenous vein	UBERON:0007318	87.27	gold quality
right lobe of liver	UBERON:0001114	87.25	gold quality
ventral tegmental area	UBERON:0002691	87.19	gold quality
tibial artery	UBERON:0007610	87.11	gold quality
popliteal artery	UBERON:0002250	87.09	gold quality
inferior vagus X ganglion	UBERON:0005363	86.96	gold quality
right atrium auricular region	UBERON:0006631	86.92	gold quality
hypothalamus	UBERON:0001898	86.91	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.96
E-MTAB-6386	no	275.24

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 80 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Vagina	tissue	36.7	low
Esophagus	tissue	36.1	medium
Skin 1	tissue	31.6	low
Locus coeruleus	tissue	18.8
Hippocampus	tissue	18.3	medium
Ovary	tissue	17.5	low
Tonsil	tissue	16.8	medium
Caudate putamen	tissue	16.4
Nucleus accumbens	tissue	14.0
Seminal vesicle	tissue	13.7	high
Fallopian tube	tissue	13.6	medium
Gallbladder	tissue	13.4	high
Placenta	tissue	13.3	high
Urinary bladder	tissue	13.1	high
Lung	tissue	12.8	medium
Smooth muscle	tissue	12.5	low
Thymus	tissue	12.1
Breast	tissue	11.7	high
Endometrium 1	tissue	11.7	medium
Choroid plexus	tissue	11.7
Cervix	tissue	11.4	high
Salivary gland	tissue	11.1	high
Frontal cortex	tissue	10.8
Pituitary gland	tissue	10.4
Prostate	tissue	10.4	medium
Postcentral gyrus	tissue	10.4
Adipose tissue	tissue	10.0	low
Appendix	tissue	9.4	high
Spinal cord	tissue	9.3
Lymph node	tissue	8.9	not detected
Rectum	tissue	8.4	high
Parathyroid gland	tissue	8.4	high
Colon	tissue	8.4	high
Substantia nigra	tissue	8.3
Periaqueductal gray	tissue	8.1
Spleen	tissue	7.9	not detected
Corpus callosum	tissue	7.7
Stomach 1	tissue	7.6	low
Medulla oblongata	tissue	7.6
Superior colliculi	tissue	7.1
Liver	tissue	7.1	high
Midbrain	tissue	6.8
Thyroid gland	tissue	6.7	high
Epididymis	tissue	6.5	high
Duodenum	tissue	6.5	high
Adrenal gland	tissue	6.5	medium
Pons	tissue	6.4
Thalamus	tissue	6.4
Pancreas	tissue	6.3	high
Tongue	tissue	6.3
Small intestine	tissue	6.2	high
Hypothalamus	tissue	5.9
Heart muscle	tissue	5.7	medium
Septum	tissue	5.5
Hippocampal formation	tissue	5.2
Kidney	tissue	5.1	medium
Basal ganglia	tissue	4.9	low
Ventral forebrain	tissue	4.9
Skeletal muscle	tissue	4.8	not detected
Cerebellum	tissue	4.6	low

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — Area postrema (43.0), Inferior olive (31.2), Cervical spinal cord, central gray (30.2), Nucleus gracilis (30.2), Nucleus rhomboideus (29.6).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): EWSR1, FLI1, NFKB

miRNA regulators (miRDB)

Targeting PLD2 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

29 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-3202	99.66	67.70	2737
HSA-MIR-4516	99.61	67.78	3390
HSA-MIR-1249-5P	99.61	66.55	2049
HSA-MIR-6797-5P	99.61	66.55	2084
HSA-MIR-486-3P	99.51	66.82	1901
HSA-MIR-203A-3P	99.49	70.56	2806
HSA-MIR-4441	99.49	66.56	3216
HSA-MIR-4786-3P	99.36	68.35	1390
HSA-MIR-6734-3P	99.15	66.27	1627
HSA-MIR-3619-5P	99.00	68.87	2308
HSA-MIR-6846-5P	98.81	65.86	1121
HSA-MIR-6848-5P	98.81	65.49	1126
HSA-MIR-214-3P	98.71	68.12	2128
HSA-MIR-761	98.71	68.07	2051
HSA-MIR-4290	98.51	65.17	907
HSA-MIR-6880-5P	98.08	65.59	1282
HSA-MIR-6855-5P	97.51	66.03	830
HSA-MIR-1910-5P	97.42	66.36	844
HSA-MIR-212-5P	96.83	67.43	950
HSA-MIR-3189-3P	96.80	66.34	896
HSA-MIR-3170	95.84	64.32	721
HSA-MIR-887-3P	94.03	63.71	71
HSA-MIR-6750-5P	93.94	66.68	797
HSA-MIR-6822-5P	93.94	66.34	812

Functional genomics

gnomAD constraint: pLI 1.58e-23, LOEUF 0.933, missense Z 1.07 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000263088 — one region, missense o/e 0.95.

Literature-anchored findings (GeneRIF, showing 40)

• activation of phospholipases D1 and D2 by S1P regulates the phosphorylation of extracellular-signal-regulated kinase and IL-8 secretion in Beas-2B cells (PMID:12149127)
• localizes to the plasma membrane of mast cells; stimulated by oleic acid (PMID:12374567)
• PLD2 activity is directly regulated by ADP-ribosylation factor 4, and this ARF4-mediated PLD2 activation stimulates AP-1-dependent transcription in the EGF-induced cellular response (PMID:12446727)
• PLD is regulated py phosphoinositides through the PH domain and the polybasic motif (PMID:12486109)
• PLD2 may play a key role in the regulation of agonist-induced endocytosis of the mu-opioid receptor (PMID:12519790)
• Phospholipase D(2) gene is a susceptibility locus for colorectal cancer in Japanese individuals. (PMID:12601529)
• elevated PLD activity generates survival signals allowing cells to overcome default apoptosis programs (PMID:12615079)
• PLD isozymes stimulate cell growth by repressing expression of p21 gene (PMID:12782287)
• phospholipase D2 was enriched in caveolae; PLD2 could be involved in MEK/ERK signaling cascades that are induced by the VEGF/VEGFR-2/PKC-delta pathway in endothelial cells (PMID:14704231)
• PLD2 functions at the plasma membrane to facilitate endocytosis of the angiotensin II type 1 receptor. (PMID:14718562)
• The phospholipase D2 possesses a PH domain, activation by phosphatidylinositol 4,5-disphosphate (PIP2) involves binding to a conserved cluster of basic residues. (PMID:15052337)
• Translocation of PLD2 to EGF-induced membrane ruffles has been observed in HeLa cells when coexpressed with PIP kinase Ialpha. (PMID:15052340)
• phospholipase D isozymes mediate EGCG-induced COX-2 expression through PKC and p38 in immortalized astroglial line and normal astrocyte cells (PMID:15210717)
• findings provide the first description of a mechanism for activation phospholipase D2 in a physiological setting and of a role for Fyn and Fgr in Fc epsilon RI-mediated signaling. (PMID:15282299)
• an increase in local membrane monomeric tubulin concentration inhibits PLD2 activity (PMID:15548524)
• ANP recruits a signal pathway associated with p38 MAPK, NHE-1 and PLD responsible for ROS production, suggesting a possible role for ANP as novel modulator of ROS generation in HepG2 cells (PMID:15665518)
• Phospholipase D2 (PLD2) enhances PKCzeta activity through direct interaction in a lipase activity-independent manner. (PMID:15798205)
• EWS-Fli1 may play a role in the regulation of PDGF-induced tumor proliferation-signaling enzymes via PLD2 expression in Ewing sarcoma cells (PMID:15919668)
• intracellular unsaturated acyl-CoA derivatives destabilize ABCA1 by activating a PLD2 signaling pathway (PMID:16118212)
• These results suggest that intact phosphorylation sites within the MARCKS ED are required for PLD activation and influence both membrane-cytoskeletal organization and cell viability. (PMID:16341931)
• Y(169) & Y(179) are in 2 consensus sites in PLD2 mediating SH2 interaction with Grb2. They are needed for recruiting Sos, but only overexpression of the PLD2 Y179F mutant resulted in more Ras activity, p44/42(Erk) phosphorylation & enhanced DNA synthesis. (PMID:16407827)
• PLD functions as a GTPase activating protein (GAP) through its phox homology domain (PX), which directly activates the GTPase domain of dynamin and increased epidermal growth factor receptor (EGFR) endocytosis at physiological EGF concentrations. (PMID:16622417)
• Data show that the G–>A (Gly901Asp) mutation of the human PLD2 gene results in catalytic inactivation of the encoded protein. (PMID:16824927)
• demonstration of the involvement of PLD1 and PLD2 and its enzymatic activity toward chemokines in the key physiologic process of leukocyte migration (PMID:16873675)
• gene expression is increased by EWS.Fli-1 and FLI-1 by binding to an erythroblast transformation-specific domain of the PLC2 promoter (PMID:16964281)
• Our findings establish a crucial role for PLD2 in the coupling of extracellular signals to Sos-mediated Ras activation, and provide new insights into the spatial coordination of this activation event. (PMID:17486115)
• Thus, LFA-1 acts through PLD2 to reshape the pattern of Ras activation downstream of the TCR (PMID:17486117)
• Plays a major role in promoting HIV-1 long terminal repeat transactivation and virus replication. (PMID:17627030)
• These results demonstrate for the first time that PLD1 and PLD2 isozymes enhance cobalt chlorde-induced COX-2 expression through differential signaling pathways in astroglioma cells. (PMID:17640750)
• Elevated phospholipase D2 is associated with colorectal carcinoma (PMID:17914593)
• Data suggest that recombinant human phospholipase D2 alone cannot induce apoptosis in HL-60 cells, but it can potentiate the apoptosis of HL-60 cells induced by camptothecin. (PMID:17977756)
• These findings indicate the involvement of phospholipase D activation in hBD-2 up-regulation in gingival epithelial cells. (PMID:17986621)
• Protein kinase C-epsilon regulates sphingosine 1-phosphate-mediated migration of human lung endothelial cells through activation of phospholipase D2, protein kinase C-zeta, and Rac1 (PMID:18296444)
• depletion of phospholipase D2 inhibited motility more severely, essential for the maintenance of keratocyte-like locomotion of NBT-II cells, presumably by regulating the actin cytoskeleton. (PMID:18344600)
• Data suggest that PLD2 is an early player upstream of the Ras-ERK1/2-IL-2 pathway in T-cells via phosphatidic acid and diacylglycerol production. (PMID:18423386)
• we present evidence for the presence of both PLD1 and PLD2 in platelets and indicate a role in platelet activation. (PMID:18432522)
• Expression of active PLD2 enhances processes favorable to lymphoma cell metastasis, whereas expression of inactive PLD2 inhibits metastasis. (PMID:18523140)
• The study results suggest that PLD2 is a new substrate of Cdk5 and that the phosphorylation of PLD2 by Cdk5 is involved in epidermal growth factor-dependent insulin secretion. (PMID:18625302)
• Phospholipase D2 is cleaved at two or three sites in the front of N-terminus and maintained anti-apoptotic potency in spite of its cleavage during apoptosis. (PMID:18694819)
• These results demonstrate a role of PLD in hyperoxia-mediated IQGAP1 activation through Rac1 in tyrosine phosphorylation of Src and cortactin, as well as in p47(phox) translocation and reactive oxygen species formation in human lung endothelial cells. (PMID:19366706)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	pld2	ENSDARG00000034262
mus_musculus	Pld2	ENSMUSG00000020828
rattus_norvegicus	Pld2	ENSRNOG00000019604
drosophila_melanogaster	Pld	FBGN0286511
caenorhabditis_elegans		WBGENE00004040

Paralogs (1): PLD1 (ENSG00000075651)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:892877) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 3 distinct phenotype terms.

Mouse phenotype (MP)	Records
abnormal lipid level	1
abnormal neutrophil physiology	1
abnormal response/metabolism to endogenous compounds	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Bos taurus	Q0V8L6	92.3%	Diamond
Cricetulus griseus	O08684	90.7%	Diamond
Arabidopsis thaliana	Q9M9W8	63.4%	Diamond
Saccharomyces cerevisiae S288C	P36126	40.1%	Diamond
Dictyostelium discoideum	Q54UK0	39.9%	Diamond
Phytophthora infestans	Q5BMR2	39.3%	Diamond
Schizosaccharomyces pombe 972h-	Q09706	37.9%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
C17orf107	protein-coding	100130311
CHRNE	protein-coding	1145
C17orf114	protein-coding	119139905
MINK1	protein-coding	50488
GP1BA	protein-coding	2811
GLTPD2	protein-coding	388323
PSMB6	protein-coding	5694
VMO1	protein-coding	284013

Protein

Protein identifiers

Phospholipase D2 — O14939 (reviewed: O14939)

Alternative names: Choline phosphatase 2, PLD1C, Phosphatidylcholine-hydrolyzing phospholipase D2

All UniProt accessions (6): I3L1F3, I3L222, I3L381, I3L3I7, I3L4R5, O14939

UniProt curated annotations — full annotation on UniProt →

Function. Function as phospholipase selective for phosphatidylcholine. May have a role in signal-induced cytoskeletal regulation and/or endocytosis.

Subunit / interactions. Interacts with PIP5K1B. Interacts with EGFR.

Subcellular location. Cell membrane.

Tissue specificity. Ubiquitous.

Post-translational modifications. Phosphorylated by FGR.

Activity regulation. Stimulated by phosphatidylinositol 4,5-bisphosphate and slightly activated by the ADP-ribosylation factor-1 (ARF-1).

Similarity. Belongs to the phospholipase D family.

Isoforms (3)

UniProt ID	Names	Canonical?
O14939-1	PLD2A	yes
O14939-3	PLD2C
O14939-4	PLD2B

RefSeq proteins (2): NP_001230037, NP_002654* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001683	PX_dom	Domain
IPR001736	PLipase_D/transphosphatidylase	Domain
IPR001849	PH_domain	Domain
IPR011993	PH-like_dom_sf	Homologous_superfamily
IPR015679	PLipase_D_fam	Family
IPR016555	PLipase_D_euk	Family
IPR025202	PLD-like_dom	Domain
IPR036871	PX_dom_sf	Homologous_superfamily

Pfam: PF00614, PF00787, PF13091

Enzyme classification (BRENDA)

• EC 3.1.4.4 — phospholipase D (BRENDA: 94 organisms, 465 substrates, 320 inhibitors, 67 Km, 27 kcat entries)
• EC 4.2.1.1 — carbonic anhydrase (BRENDA: 178 organisms, 196 substrates, 2137 inhibitors, 263 Km, 291 kcat entries)

Substrate kinetics (BRENDA)

30 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
CO2	0.012–4700	194
PHOSPHATIDYLCHOLINE	0.0015–2.5	18
N-PALMITOYL-PHOSPHATIDYLETHANOLAMINE	0.0029–0.045	16
4-NITROPHENYL ACETATE	0.0024–30.53	16
H2CO3	0.434–112.7	16
DIOLEOYL-PHOSPHATIDYLCHOLINE	0.0015–3	4
LYSOPHOSPHATIDYLCHOLINE	1–3	4
HCO3-	9.3–37	4
P-NITROPHENYL ACETATE	3.86–6.8	4
EGG PHOSPHATIDYLCHOLINE	30.2–33.17	2
L-ALPHA-PHOSPHATIDYLCHOLINE	2.71–3.44	2
PHOSPHATIDYL-P-NITROPHENOL	0.075–1.16	2
PHOSPHATIDYLETHANOLAMINE	0.91–4	2
4-NITROPHENYL PHOSPHATE	0.935–2.195	2
1,2-DIBUTYL-SN-GLYCERO-3-PHOSPHOCHOLINE	0.16	1

Catalyzed reactions (Rhea)

• a 1,2-diacyl-sn-glycero-3-phosphocholine + H2O = a 1,2-diacyl-sn-glycero-3-phosphate + choline + H(+) (RHEA:14445)
• 1,2-dihexadecanoyl-sn-glycero-3-phosphocholine + H2O = 1,2-dihexadecanoyl-sn-glycero-3-phosphate + choline + H(+) (RHEA:44872)

UniProt features (80 total): strand 23, helix 23, sequence conflict 10, sequence variant 7, turn 7, domain 4, region of interest 3, splice variant 2, chain 1

Structure

Experimental structures (PDB)

6 structures by resolution:

PDB	Title	Method	Resolution (Å)
6OHM	Structure of tungstate bound human Phospholipase D2 catalytic domain	X-RAY DIFFRACTION	1.9
6OHO	Structure of human Phospholipase D2 catalytic domain	X-RAY DIFFRACTION	2
6OHP	Structure of compound 1 (halopemide) bound human Phospholipase D2 catalytic domain	X-RAY DIFFRACTION	2.6
6OHQ	Structure of compound 4 bound human Phospholipase D2 catalytic domain	X-RAY DIFFRACTION	2.69
7SVP	Structure of compound 34 bound to human Phospholipase D2 catalytic domain	X-RAY DIFFRACTION	2.9
6OHS	Structure of compound 3 (ML299) bound human Phospholipase D2 catalytic domain	X-RAY DIFFRACTION	3.2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O14939-F1	89.55	0.75

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Hydrolases, Metabolic proteins, Predicted intracellular proteins, RAS pathway related proteins

Protein evidence: Evidence at protein level

Antibody reliability (HPA): IH approved

Function

Pathways and Gene Ontology

Reactome pathways

4 curated (TAS) of 16; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

16 pathways:

ID	Pathway	Evidence
R-HSA-9013149	RAC1 GTPase cycle	curated
R-HSA-9013404	RAC2 GTPase cycle	curated
R-HSA-2029485	Role of phospholipids in phagocytosis	curated
R-HSA-1483166	Synthesis of PA	curated
R-HSA-2029480	Fcgamma receptor (FCGR) dependent phagocytosis	—
R-HSA-1483206	Glycerophospholipid biosynthesis	—
R-HSA-168256	Immune System	—
R-HSA-168249	Innate Immune System	—
R-HSA-1430728	Metabolism	—
R-HSA-556833	Metabolism of lipids	—
R-HSA-1483257	Phospholipid metabolism	—
R-HSA-9012999	RHO GTPase cycle	—
R-HSA-162582	Signal Transduction	—
R-HSA-194315	Signaling by Rho GTPases	—
R-HSA-9716542	Signaling by Rho GTPases, Miro GTPases and RHOBTB3	—
R-HSA-1483148	Synthesis of PG	electronic

MSigDB gene sets: 173 (showing top): GOBP_G_PROTEIN_COUPLED_RECEPTOR_INTERNALIZATION, GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, REACTOME_INNATE_IMMUNE_SYSTEM, ENK_UV_RESPONSE_KERATINOCYTE_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_SYNAPTIC_VESICLE_RECYCLING, GOBP_REGULATION_OF_VESICLE_MEDIATED_TRANSPORT, GOBP_PHOSPHOLIPID_BIOSYNTHETIC_PROCESS, PID_RHOA_PATHWAY, PID_ARF6_DOWNSTREAM_PATHWAY, GOBP_GLYCEROLIPID_METABOLIC_PROCESS

GO Biological Process (10): phosphatidic acid biosynthetic process (GO:0006654), cytoskeleton organization (GO:0007010), small GTPase-mediated signal transduction (GO:0007264), phospholipid catabolic process (GO:0009395), synaptic vesicle recycling (GO:0036465), Fc-gamma receptor signaling pathway involved in phagocytosis (GO:0038096), regulation of vesicle-mediated transport (GO:0060627), lipid metabolic process (GO:0006629), lipid catabolic process (GO:0016042), intracellular signal transduction (GO:0035556)

GO Molecular Function (5): D-type glycerophospholipase activity (GO:0004630), phosphatidylinositol binding (GO:0035091), catalytic activity (GO:0003824), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (6): endoplasmic reticulum membrane (GO:0005789), plasma membrane (GO:0005886), cytoplasmic vesicle (GO:0031410), brush border membrane (GO:0031526), presynapse (GO:0098793), membrane (GO:0016020)

Reactome top-level categories

11 top-level categories:

Category	Pathways
Glycerophospholipid biosynthesis	2
RHO GTPase cycle	2
Fcgamma receptor (FCGR) dependent phagocytosis	1
Phospholipid metabolism	1
Metabolism of lipids	1
Immune System	1
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1
Innate Immune System	1
Metabolism	1
Signaling by Rho GTPases	1
Signal Transduction	1

GO top-level categories

39 GO namespaces:

Category	Terms
cellular anatomical structure	2
phosphatidic acid metabolic process	1
glycerophospholipid biosynthetic process	1
organelle organization	1
intracellular signaling cassette	1
phospholipid metabolic process	1
lipid catabolic process	1
organophosphate catabolic process	1
transport	1
establishment of localization in cell	1
synaptic vesicle cycle	1
Fc receptor mediated stimulatory signaling pathway	1
phagocytosis	1
Fc-gamma receptor signaling pathway	1
vesicle-mediated transport	1
regulation of cellular process	1
regulation of transport	1
primary metabolic process	1
lipid metabolic process	1
catabolic process	1
intracellular anatomical structure	1
signal transduction	1
glycerophospholipase activity	1
phosphoric diester hydrolase activity	1
anion binding	1
molecular_function	1
binding	1
catalytic activity	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
membrane	1
cell periphery	1
cytoplasm	1
intracellular vesicle	1
brush border	1
apical plasma membrane	1
cell projection membrane	1
synapse	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 1 of 21 annotations. The rest are phylogenetic / computational / electronic (IEA).

1 experimentally-supported GO terms:

GO term	NS	Evidence
plasma membrane	CC	direct assay

Protein interactions and networks

STRING

showing 15 of 1,482 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PLD2	NAPEPLD	Q6IQ20	910
PLD2	GPLD1	P80108	819
PLD2	DOCK2	Q92608	800
PLD2	ARF1	P10947	746
PLD2	ARF6	P26438	648
PLD2	RAC2	P15153	628
PLD2	PLD3	Q8IV08	597
PLD2	RABIF	P47224	581
PLD2	PLD5	Q8N7P1	572
PLD2	SDCBP	O00560	547
PLD2	DOCK1	Q14185	539
PLD2	SMPD2	O60906	534
PLD2	PLD6	Q8N2A8	518
PLD2	PLD4	Q96BZ4	495
PLD2	RALA	P11233	484

IntAct

Human interaction partners of PLD2 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

30 partners by confidence:

Partner	Interaction type	MIscore	Records
RAC2	direct interaction	0.650	4
GRB2	physical association	0.640	4
DNAJC7	association	0.640	3
GPR156	association	0.640	3
SPC24	association	0.640	1
TUBB	association	0.640	1
APP	physical association	0.560	3
UNG	physical association	0.560	3
CFL1	direct interaction	0.540	2
CCDC107	association	0.530	3
CDK5RAP3	association	0.530	3
CHRM3	association	0.530	1
KBTBD7	association	0.530	1
TUBA4A	association	0.530	1
KBTBD6	association	0.350	2
ASIC2	association	0.350	1
BSND	association	0.350	1
CACNG7	association	0.350	1
CIB2	association	0.350	1
DDR2	association	0.350	1
DNAJB5	association	0.350	1
HEATR3	association	0.350	1
MFSD11	association	0.350	1
SLC16A7	association	0.350	1
SLC38A2	association	0.350	1
TEX264	association	0.350	1
TNFRSF19	association	0.350	1
TTC9C	association	0.350	1
TUBB4B	association	0.350	1
FTSJ1	physical association	0.000	1

BioGRID (184 interactions; top human partners by supporting records): CDH5 (Affinity Capture-MS; 4 records), AMPH (Phenotypic Suppression; 3 records), ANKMY2 (Affinity Capture-Western; 3 records), CAV1 (Affinity Capture-Western; 3 records), DNAJC7 (Affinity Capture-MS; 3 records), HIF1A (Affinity Capture-Western; 3 records), SPC24 (Affinity Capture-MS; 3 records), SRC (Biochemical Activity; 3 records), VHL (Affinity Capture-Western; 3 records), ALDOA (Reconstituted Complex; 2 records), AQP3 (Affinity Capture-Western; 2 records), ARF1 (Reconstituted Complex; 2 records), BAG2 (Affinity Capture-MS; 2 records), BIN1 (Phenotypic Suppression; 2 records), CACNG5 (Affinity Capture-MS; 2 records)

SIGNOR signaling

showing 10 of 11 signaling interactions:

A	Effect	B	Mechanism
PRKCA	up-regulates	PLD2	phosphorylation
JAK3	up-regulates	PLD2	phosphorylation
PRKCD	up-regulates	PLD2	phosphorylation
EGFR	“up-regulates activity”	PLD2	phosphorylation
P2RX7	up-regulates	PLD2
PLD2	up-regulates	ERK1/2
CDK5	“down-regulates activity”	PLD2	phosphorylation
CDK5	“up-regulates activity”	PLD2	phosphorylation
PTK2	“up-regulates activity”	PLD2	phosphorylation
GNAI1	down-regulates	PLD2	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 30 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Adaptive Immune System	5	6.8×	4e-03

Disease & clinical

Genetic variants

Variant evidence for PLD2: 187 ClinVar records (0 pathogenic / likely pathogenic); 3 GWAS associations.

ClinVar

187 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	145
Likely benign	7
Benign	6

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 24 predictions of 2,090):

Position(s)	Effect	Δscore	Sites
17:4807770	acceptor_loss	1.0000	3
17:4807882–4807883	donor_loss	1.0000	5
17:4807891	donor_gain	1.0000
17:4808135	donor_gain	1.0000
17:4808273	acceptor_loss	1.0000
17:4808394	donor_gain	1.0000
17:4808417–4808418	donor_loss	1.0000	5
17:4809292	acceptor_gain	1.0000
17:4809364–4809365	donor_loss	1.0000	5
17:4809677	acceptor_gain	1.0000

AlphaMissense

2,404 missense substitutions predicted likely pathogenic (of 6,069 scored), across 587 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
D459	8	0.995	0.999
D784	8	0.992	0.998
H442	8	0.991	0.996
D510	8	0.991	0.998
D542	8	0.990	0.997
H756	8	0.987	0.995
F643	8	0.985	1.000
H441	8	0.982	0.997
D466	8	0.981	0.995
N773	8	0.979	1.000
S778	8	0.977	0.999
D776	8	0.972	0.996
N641	8	0.970	0.999
N655	8	0.968	0.998
F188	8	0.967	0.998
F687	8	0.966	0.997
N775	8	0.964	0.999
D518	8	0.963	0.989
D764	8	0.963	0.991
D384	8	0.957	0.983

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

1 prognostic cancer types:

Cancer	Prognostic	p-value
Ovary Serous Cystadenocarcinoma (TCGA)	unfavorable	0.000107

Disease associations

OMIM: gene MIM:602384 | disease phenotypes:

GWAS associations

3 associations:

Study	Trait	p-value
GCST001413_9	Sphingolipid levels	1e-9
GCST003155_20	Systemic lupus erythematosus	3e-9
GCST003156_46	Systemic lupus erythematosus	3e-6

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2734 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 79,240 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

2 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL81	RALOXIFENE	4	78,815
CHEMBL245621	HALOPEMIDE	2	425

PharmGKB: 1 entry (CPIC guideline: no)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — Hydrolases & Lipases

Most potent curated ligand interactions (3 total), top 3:

Ligand	Action	Affinity	Parameter
FIPI	Inhibition	7.77	pIC50
VU0364739	Inhibition	7.7	pIC50
compound 69 [PMID: 19136975]	Inhibition	6.03	pIC50

Binding affinities (BindingDB)

679 measured of 737 human assays (772 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
cid_44573642	IC50	1 nM
CHEMBL4453586	IC50	1 nM
N-[(2S)-1-[4-(2-oxo-3H-benzimidazol-1-yl)piperidin-1-yl]propan-2-yl]-1H-indole-2-carboxamide	IC50	1 nM
5-fluoranyl-N-[(2S)-1-[4-(2-oxidanylidene-3H-benzimidazol-1-yl)piperidin-1-yl]propan-2-yl]-1H-indole-2-carboxamide	IC50	1 nM
(S)-N-(1-(4-(6-fluoro-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)piperidin-1-yl)propan-2-yl)-2-naphthamide	IC50	2 nM
CHEMBL2304616	IC50	2 nM
cid_53470042	IC50	2 nM
N-[(2R)-1-[4-(5-chloro-2-oxo-3H-benzimidazol-1-yl)-1-piperidinyl]propan-2-yl]-1H-indole-2-carboxamide;2,2,2-trifluoroacetic acid	IC50	2 nM
VU0361535-1	IC50	2 nM
N-[(2S)-1-[4-(2-oxo-3H-benzimidazol-1-yl)piperidin-1-yl]propan-2-yl]-2-phenoxyacetamide;2,2,2-trifluoroacetic acid	IC50	2 nM
cid_53470207	IC50	2 nM
(S)-N-(1-(4-(5-chloro-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)piperidin-1-yl)propan-2-yl)-3,4-difluorobenzamide	IC50	3 nM
cid_44573690	IC50	3 nM
VU0404360-1	IC50	3 nM
N-[(2S)-1-[4-(5-chloro-2-oxo-3H-benzimidazol-1-yl)-1-piperidinyl]propan-2-yl]-3,4-difluorobenzamide;2,2,2-trifluoroacetic acid	IC50	3 nM
N-[(2S)-1-[4-(6-fluoro-2-oxo-3H-benzimidazol-1-yl)piperidin-1-yl]propan-2-yl]naphthalene-2-carboxamide;2,2,2-trifluoroacetic acid	IC50	3 nM
(S)-N-(1-(4-(5-bromo-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)piperidin-1-yl)propan-2-yl)-3,4-difluorobenzamide	IC50	3.5 nM
(S)-N-(1-(4-(5-bromo-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)piperidin-1-yl)propan-2-yl)-4-chlorobenzamide	IC50	4 nM
cid_44573687	IC50	4 nM
cid_21428895	IC50	4 nM
N-[(2S)-1-[4-(5-bromo-2-oxo-3H-benzimidazol-1-yl)piperidin-1-yl]propan-2-yl]-4-chlorobenzamide;2,2,2-trifluoroacetic acid	IC50	4 nM
N-[(2S)-1-[4-(5-bromo-2-oxo-3H-benzimidazol-1-yl)piperidin-1-yl]propan-2-yl]-4-fluorobenzamide;2,2,2-trifluoroacetic acid	IC50	4 nM
N-[(2S)-1-[4-(5-bromo-2-oxo-3H-benzimidazol-1-yl)piperidin-1-yl]propan-2-yl]-3,4-difluorobenzamide;2,2,2-trifluoroacetic acid	IC50	4 nM
VU0359566-1	IC50	4 nM
4-chloro-N-[2-[4-(5-iodo-2-oxo-3H-benzimidazol-1-yl)-1-piperidinyl]ethyl]benzamide;2,2,2-trifluoroacetic acid	IC50	5 nM
N-[(2S)-1-[1-[3,4-bis(fluoranyl)phenyl]-4-oxidanylidene-1,3,8-triazaspiro[4.5]decan-8-yl]propan-2-yl]-5-fluoranyl-1H-indole-2-carboxamide;2,2,2-tris(fluoranyl)ethanoic acid	IC50	5 nM
3,4-bis(fluoranyl)-N-[(2S)-1-[4-(6-fluoranyl-2-oxidanylidene-3H-benzimidazol-1-yl)piperidin-1-yl]propan-2-yl]benzamide;2,2,2-tris(fluoranyl)ethanoic acid	IC50	5 nM
(S)-N-(1-(4-(5-bromo-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)piperidin-1-yl)propan-2-yl)-2-naphthamide	IC50	5.5 nM
2-(4-hydroxyphenyl)-3-({4-[2-(piperidin-1-yl)ethoxy]phenyl}carbonyl)-1-benzothiophen-6-ol	IC50	5.7 nM
4-chloranyl-N-[(2S)-1-[4-(5-chloranyl-2-oxidanylidene-3H-benzimidazol-1-yl)piperidin-1-yl]propan-2-yl]benzamide;2,2,2-tris(fluoranyl)ethanoic acid	IC50	6 nM
(S)-4-chloro-N-(1-(4-(5-chloro-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)piperidin-1-yl)propan-2-yl)benzamide	IC50	6.4 nM
Halopemide	IC50	7 nM
N-[(2S)-3-methyl-1-(4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decan-8-yl)butan-2-yl]-1H-indole-2-carboxamide;2,2,2-trifluoroacetic acid	IC50	7 nM
N-[(2S)-1-[4-(5-bromanyl-2-oxidanylidene-3H-benzimidazol-1-yl)piperidin-1-yl]propan-2-yl]-4-methyl-benzamide;2,2,2-tris(fluoranyl)ethanoic acid	IC50	7 nM
4-chloranyl-N-[(2S)-1-[4-(5-fluoranyl-2-oxidanylidene-3H-benzimidazol-1-yl)piperidin-1-yl]propan-2-yl]benzamide;2,2,2-tris(fluoranyl)ethanoic acid	IC50	7 nM
VU0249424-1	IC50	7 nM
(S)-4-chloro-N-(1-(4-(5-fluoro-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)piperidin-1-yl)propan-2-yl)benzamide	IC50	7.4 nM
racemic trans-N-((S)-1-(4-(5-chloro-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)piperidin-1-yl)propan-2-yl)-2-phenylcyclopropanecarboxamide	IC50	8 nM
N-[(2S)-1-[4-(6-fluoranyl-2-oxidanylidene-3H-benzimidazol-1-yl)piperidin-1-yl]propan-2-yl]-4-methyl-benzamide;2,2,2-tris(fluoranyl)ethanoic acid	IC50	8 nM
N’-[(2S)-1-[5-(2-bromo-5-cyanophenyl)-2-oxo-1-oxa-3,4-diazaspiro[5.5]undec-4-en-9-yl]propan-2-yl]oxamide	IC50	9 nM	US-20240101572: DIHYDROOXADIAZINONE COMPOUND AND PHARMACEUTICAL USE THEREOF
N-[2-[4-(5-iodo-2-oxo-3H-benzimidazol-1-yl)-1-piperidinyl]ethyl]-2-phenyl-1-cyclopropanecarboxamide;2,2,2-trifluoroacetic acid	IC50	9 nM
cid_21429000	IC50	10 nM
(S)-N-(1-(4-(5-chloro-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)piperidin-1-yl)propan-2-yl)-4-fluorobenzamide	IC50	10 nM
(S)-N-(1-(1-(3-fluorophenyl)-4-oxo-1,3,8-triazaspiro[4.5]decan-8-yl)propan-2-yl)-2-naphthamide	IC50	10 nM
N’-[(2S)-1-[5-(2-bromo-4-fluorophenyl)-2-oxo-1-oxa-3,4-diazaspiro[5.5]undec-4-en-9-yl]propan-2-yl]-N-methyloxamide	IC50	10 nM	US-20240101572: DIHYDROOXADIAZINONE COMPOUND AND PHARMACEUTICAL USE THEREOF
N-[(2S)-1-[5-[2-bromo-4-(2-hydroxy-2-methylpropoxy)phenyl]-2-oxo-1-oxa-3,4-diazaspiro[5.5]undec-4-en-9-yl]propan-2-yl]-3-chloro-1,2-oxazole-5-carboxamide	IC50	10 nM	US-20240101572: DIHYDROOXADIAZINONE COMPOUND AND PHARMACEUTICAL USE THEREOF
N-cyclopropyl-N’-[(2S)-1-[5-(4-fluoro-2-iodophenyl)-2-oxo-1-oxa-3,4-diazaspiro[5.5]undec-4-en-9-yl]propan-2-yl]oxamide	IC50	10 nM	US-20240101572: DIHYDROOXADIAZINONE COMPOUND AND PHARMACEUTICAL USE THEREOF
N-[(2S)-1-[5-(2-bromo-4-cyanophenyl)-2-oxo-1-oxa-3,4-diazaspiro[5.5]undec-4-en-9-yl]propan-2-yl]-5-methyl-1H-pyrazole-3-carboxamide	IC50	10 nM	US-20240101572: DIHYDROOXADIAZINONE COMPOUND AND PHARMACEUTICAL USE THEREOF
N-[(2S)-1-[5-(2,5-dichlorophenyl)-2-oxo-1-oxa-3,4-diazaspiro[5.5]undec-4-en-9-yl]propan-2-yl]indolizine-2-carboxamide	IC50	10 nM	US-20240101572: DIHYDROOXADIAZINONE COMPOUND AND PHARMACEUTICAL USE THEREOF
N-[(2S)-1-[1-(3-fluorophenyl)-4-oxo-1,3,8-triazaspiro[4.5]decan-8-yl]propan-2-yl]naphthalene-2-carboxamide;2,2,2-trifluoroacetic acid	IC50	10 nM

ChEMBL bioactivities

179 potent at pChembl≥5 of 186 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.60	IC50	2.5	nM	CHEMBL4475943
7.92	IC50	12	nM	CHEMBL4453586
7.85	IC50	14	nM	CHEMBL492972
7.82	IC50	15.15	nM	CHEMBL5555701
7.77	IC50	17	nM	CHEMBL398567
7.70	IC50	20	nM	CHEMBL2325485
7.70	IC50	20	nM	CHEMBL3925090
7.70	IC50	20	nM	CHEMBL4446255
7.70	IC50	20	nM	CHEMBL1254577
7.70	IC50	20	nM	CHEMBL398567
7.70	IC50	20	nM	CHEMBL246240
7.60	IC50	25	nM	CHEMBL1254736
7.58	IC50	26	nM	CHEMBL4594070
7.52	IC50	30	nM	CHEMBL471257
7.52	IC50	30	nM	CHEMBL1253900
7.46	IC50	35	nM	CHEMBL2325482
7.40	IC50	40	nM	CHEMBL1253820
7.38	IC50	42	nM	CHEMBL246032
7.38	IC50	42	nM	CHEMBL492971
7.37	IC50	43	nM	CHEMBL4436548
7.36	IC50	44	nM	CHEMBL2137046
7.30	IC50	50	nM	CHEMBL1254081
7.22	IC50	60	nM	CHEMBL3923136
7.22	IC50	60	nM	CHEMBL1254495
7.21	IC50	61	nM	CHEMBL523162
7.20	IC50	63	nM	CHEMBL1254653
7.19	IC50	64	nM	CHEMBL5085284
7.17	IC50	67	nM	CHEMBL4446255
7.16	IC50	70	nM	CHEMBL4515874
7.16	IC50	70	nM	CHEMBL1254823
7.16	IC50	70	nM	CHEMBL1254996
7.14	IC50	73	nM	CHEMBL1254908
7.12	IC50	76	nM	CHEMBL521990
7.10	IC50	79	nM	CHEMBL1213144
7.10	IC50	80	nM	CHEMBL1255082
7.08	IC50	84	nM	CHEMBL2325485
7.05	IC50	90	nM	CHEMBL471054
7.01	IC50	97	nM	CHEMBL492561
7.00	IC50	100	nM	CHEMBL3925090
7.00	IC50	100	nM	CHEMBL1255081
7.00	IC50	100	nM	CHEMBL1254176
6.96	IC50	110	nM	CHEMBL511475
6.94	IC50	115	nM	CHEMBL4570440
6.92	IC50	120	nM	CHEMBL2325487
6.92	IC50	120	nM	CHEMBL1254909
6.89	IC50	130	nM	CHEMBL1213097
6.89	IC50	130	nM	CHEMBL1213067
6.85	IC50	140	nM	CHEMBL4448918
6.85	IC50	140	nM	CHEMBL493010
6.85	IC50	140	nM	CHEMBL471056

PubChem BioAssay actives

209 with measured affinity, of 283 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
N-[2-[(4S)-4-(4-fluorophenyl)-1-oxo-2,8-diazaspiro[4.5]decan-8-yl]ethyl]-1H-indole-2-carboxamide	1532925: Inhibition of GFP-fused PLD2 (unknown origin) expressed in HEK293 cells by cellular assay	ic50	0.0025	uM
N-[(2S)-1-[(4S)-4-(4-fluorophenyl)-1-oxo-2,8-diazaspiro[4.5]decan-8-yl]propan-2-yl]-1H-indole-2-carboxamide	1532925: Inhibition of GFP-fused PLD2 (unknown origin) expressed in HEK293 cells by cellular assay	ic50	0.0120	uM
3,4-difluoro-N-[2-[4-(6-fluoro-2-oxo-3H-benzimidazol-1-yl)piperidin-1-yl]ethyl]benzamide	418767: Inhibition of GFP-labelled human PLD2 HEK293 cells	ic50	0.0140	uM
5-fluoro-N-[2-[4-(2-oxo-3H-benzimidazol-1-yl)piperidin-1-yl]ethyl]-1H-indole-2-carboxamide	1800492: PLD In Vitro Kinetic Assay from Article 10.1111/cbdd.12319: “1,3-disubstituted-4-aminopyrazolo [3, 4-d] pyrimidines, a new class of potent inhibitors for phospholipase D.”	ic50	0.0150	uM
1-(4-methoxyphenyl)-3-phenylpyrazolo[3,4-d]pyrimidin-4-amine	1800492: PLD In Vitro Kinetic Assay from Article 10.1111/cbdd.12319: “1,3-disubstituted-4-aminopyrazolo [3, 4-d] pyrimidines, a new class of potent inhibitors for phospholipase D.”	ic50	0.0150	uM
5-acetyl-N-[3,5-bis(trifluoromethyl)phenyl]-1H-indole-2-carboxamide	2073772: Inhibition of PLD2 (unknown origin)	ic50	0.0152	uM
N-[2-[4-(2-oxo-3H-benzimidazol-1-yl)piperidin-1-yl]ethyl]-1H-indole-2-carboxamide	306650: Inhibition of PLD2	ic50	0.0200	uM
N-[2-[1-(3-fluorophenyl)-4-oxo-1,3,8-triazaspiro[4.5]decan-8-yl]ethyl]naphthalene-2-carboxamide	1532921: Inhibition of PLD2 (unknown origin)	ic50	0.0200	uM
4-bromo-N-[(2S)-1-[1-(3-fluorophenyl)-4-oxo-1,3,8-triazaspiro[4.5]decan-8-yl]propan-2-yl]benzamide	1532921: Inhibition of PLD2 (unknown origin)	ic50	0.0200	uM
4-bromo-N-[(2S)-1-[1-(3-methylphenyl)-4-oxo-1,3,8-triazaspiro[4.5]decan-8-yl]propan-2-yl]benzamide	729467: Inhibition of GFP-tagged PLD2 in human HEK293 cells assessed as deuterated 1-butanol incorporation pretreated for 5 mins prior to substrate addition measured after 30 mins by mass spectrometry	ic50	0.0200	uM
5-fluoro-N-[2-[1-(3-fluorophenyl)-4-oxo-1,3,8-triazaspiro[4.5]decan-8-yl]ethyl]-1H-indole-2-carboxamide	515549: Inhibition of human GST-tagged PLD2A in human HEK293 cells	ic50	0.0250	uM
N-[(2S)-1-[(4S)-4-(4-fluorophenyl)-1-oxo-2,8-diazaspiro[4.5]decan-8-yl]propan-2-yl]naphthalene-2-carboxamide	1532925: Inhibition of GFP-fused PLD2 (unknown origin) expressed in HEK293 cells by cellular assay	ic50	0.0260	uM
N-[2-(4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decan-8-yl)ethyl]-1-benzothiophene-2-carboxamide	349538: Inhibition of GFP-labeled PLD2 in human HEK293 cells	ic50	0.0300	uM
5-fluoro-N-[2-[1-(4-fluorophenyl)-4-oxo-1,3,8-triazaspiro[4.5]decan-8-yl]ethyl]-1H-indole-2-carboxamide	515549: Inhibition of human GST-tagged PLD2A in human HEK293 cells	ic50	0.0300	uM
4-fluoro-N-[(2S)-1-[1-(3-fluorophenyl)-4-oxo-1,3,8-triazaspiro[4.5]decan-8-yl]propan-2-yl]benzamide	729467: Inhibition of GFP-tagged PLD2 in human HEK293 cells assessed as deuterated 1-butanol incorporation pretreated for 5 mins prior to substrate addition measured after 30 mins by mass spectrometry	ic50	0.0350	uM
N-[2-[1-(4-fluorophenyl)-4-oxo-1,3,8-triazaspiro[4.5]decan-8-yl]ethyl]quinoline-3-carboxamide	515549: Inhibition of human GST-tagged PLD2A in human HEK293 cells	ic50	0.0400	uM
N-[2-[4-(2-oxo-3H-benzimidazol-1-yl)piperidin-1-yl]ethyl]quinoline-3-carboxamide	418767: Inhibition of GFP-labelled human PLD2 HEK293 cells	ic50	0.0420	uM
4-chloro-N-[2-[4-(6-fluoro-2-oxo-3H-benzimidazol-1-yl)piperidin-1-yl]ethyl]benzamide	418767: Inhibition of GFP-labelled human PLD2 HEK293 cells	ic50	0.0420	uM
N-[2-[(4R)-4-(4-fluorophenyl)-1-oxo-2,8-diazaspiro[4.5]decan-8-yl]ethyl]-1H-indole-2-carboxamide	1532925: Inhibition of GFP-fused PLD2 (unknown origin) expressed in HEK293 cells by cellular assay	ic50	0.0430	uM
4-[1-[4-[2-(dimethylamino)ethoxy]phenyl]-2-phenylbut-1-enyl]phenol	498478: Inhibition of GFP-tagged human PLD2 expressed in human HEK293 cells assessed as decrease in phosphatidylbutanol-[d9] production after 30 mins by mass spectrometric analysis	ic50	0.0440	uM
N-[2-[1-(4-chlorophenyl)-4-oxo-1,3,8-triazaspiro[4.5]decan-8-yl]ethyl]-5-fluoro-1H-indole-2-carboxamide	515549: Inhibition of human GST-tagged PLD2A in human HEK293 cells	ic50	0.0500	uM
N-[(2S)-1-[1-(3-fluorophenyl)-4-oxo-1,3,8-triazaspiro[4.5]decan-8-yl]propan-2-yl]naphthalene-2-carboxamide	515549: Inhibition of human GST-tagged PLD2A in human HEK293 cells	ic50	0.0600	uM
N-[2-[(4S)-4-(4-fluorophenyl)-1-oxo-2,8-diazaspiro[4.5]decan-8-yl]ethyl]quinoline-3-carboxamide	1532925: Inhibition of GFP-fused PLD2 (unknown origin) expressed in HEK293 cells by cellular assay	ic50	0.0600	uM
4-chloro-N-[2-[4-(5-fluoro-2-oxo-3H-benzimidazol-1-yl)piperidin-1-yl]ethyl]benzamide	418767: Inhibition of GFP-labelled human PLD2 HEK293 cells	ic50	0.0610	uM
N-[2-[1-(3-fluorophenyl)-4-oxo-1,3,8-triazaspiro[4.5]decan-8-yl]ethyl]quinoline-3-carboxamide	515549: Inhibition of human GST-tagged PLD2A in human HEK293 cells	ic50	0.0630	uM
4-fluoro-N-[(2S)-1-[(5R)-5-(3-fluorophenyl)-2-oxo-1-oxa-3,9-diazaspiro[5.5]undecan-9-yl]propan-2-yl]benzamide	1827971: Inhibition of PLD2 (unknown origin) expressed in human HEK cells by immunoprecipitation	ic50	0.0640	uM
N-[2-[(4S)-4-(4-fluorophenyl)-1-oxo-2,8-diazaspiro[4.5]decan-8-yl]ethyl]-3-phenylprop-2-ynamide	1532925: Inhibition of GFP-fused PLD2 (unknown origin) expressed in HEK293 cells by cellular assay	ic50	0.0700	uM
N-[2-[1-(3-chlorophenyl)-4-oxo-1,3,8-triazaspiro[4.5]decan-8-yl]ethyl]-4-fluorobenzamide	515549: Inhibition of human GST-tagged PLD2A in human HEK293 cells	ic50	0.0700	uM
N-[2-[1-(3,4-difluorophenyl)-4-oxo-1,3,8-triazaspiro[4.5]decan-8-yl]ethyl]quinoline-3-carboxamide	515549: Inhibition of human GST-tagged PLD2A in human HEK293 cells	ic50	0.0700	uM
N-[2-[1-(3-chlorophenyl)-4-oxo-1,3,8-triazaspiro[4.5]decan-8-yl]ethyl]-5-fluoro-1H-indole-2-carboxamide	515549: Inhibition of human GST-tagged PLD2A in human HEK293 cells	ic50	0.0730	uM
N-[2-[4-(5-bromo-2-oxo-3H-benzimidazol-1-yl)piperidin-1-yl]ethyl]-4-fluorobenzamide	418767: Inhibition of GFP-labelled human PLD2 HEK293 cells	ic50	0.0760	uM
3,4,5-trimethoxy-N-[2-[4-(2-oxo-3H-benzimidazol-1-yl)piperidin-1-yl]ethyl]benzamide	498478: Inhibition of GFP-tagged human PLD2 expressed in human HEK293 cells assessed as decrease in phosphatidylbutanol-[d9] production after 30 mins by mass spectrometric analysis	ic50	0.0790	uM
N-[2-[1-(4-fluorophenyl)-4-oxo-1,3,8-triazaspiro[4.5]decan-8-yl]ethyl]naphthalene-2-carboxamide	515549: Inhibition of human GST-tagged PLD2A in human HEK293 cells	ic50	0.0800	uM
N-[2-(4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decan-8-yl)ethyl]quinoline-2-carboxamide	349538: Inhibition of GFP-labeled PLD2 in human HEK293 cells	ic50	0.0900	uM
N-[2-[4-(5-bromo-2-oxo-3H-benzimidazol-1-yl)piperidin-1-yl]ethyl]-4-chlorobenzamide	418767: Inhibition of GFP-labelled human PLD2 HEK293 cells	ic50	0.0970	uM
N-[2-[1-(3,4-difluorophenyl)-4-oxo-1,3,8-triazaspiro[4.5]decan-8-yl]ethyl]-5-fluoro-1H-indole-2-carboxamide	515549: Inhibition of human GST-tagged PLD2A in human HEK293 cells	ic50	0.1000	uM
N-[2-[1-(4-bromophenyl)-4-oxo-1,3,8-triazaspiro[4.5]decan-8-yl]ethyl]-5-fluoro-1H-indole-2-carboxamide	515549: Inhibition of human GST-tagged PLD2A in human HEK293 cells	ic50	0.1000	uM
N-[2-(4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decan-8-yl)ethyl]naphthalene-2-carboxamide	349538: Inhibition of GFP-labeled PLD2 in human HEK293 cells	ic50	0.1100	uM
N-[(2S)-1-[(4S)-4-(4-fluorophenyl)-1-oxo-2,8-diazaspiro[4.5]decan-8-yl]propan-2-yl]quinoline-3-carboxamide	1532925: Inhibition of GFP-fused PLD2 (unknown origin) expressed in HEK293 cells by cellular assay	ic50	0.1150	uM
3-methyl-1-phenylpyrazolo[3,4-d]pyrimidin-4-amine	1800492: PLD In Vitro Kinetic Assay from Article 10.1111/cbdd.12319: “1,3-disubstituted-4-aminopyrazolo [3, 4-d] pyrimidines, a new class of potent inhibitors for phospholipase D.”	ic50	0.1200	uM
N-[2-[1-(3,4-difluorophenyl)-4-oxo-1,3,8-triazaspiro[4.5]decan-8-yl]ethyl]naphthalene-2-carboxamide	515549: Inhibition of human GST-tagged PLD2A in human HEK293 cells	ic50	0.1200	uM
3,4-difluoro-N-[(2S)-1-[1-(3-fluorophenyl)-4-oxo-1,3,8-triazaspiro[4.5]decan-8-yl]propan-2-yl]benzamide	729467: Inhibition of GFP-tagged PLD2 in human HEK293 cells assessed as deuterated 1-butanol incorporation pretreated for 5 mins prior to substrate addition measured after 30 mins by mass spectrometry	ic50	0.1200	uM
1-(4-methoxyphenyl)-3-naphthalen-1-ylpyrazolo[3,4-d]pyrimidin-4-amine	1800492: PLD In Vitro Kinetic Assay from Article 10.1111/cbdd.12319: “1,3-disubstituted-4-aminopyrazolo [3, 4-d] pyrimidines, a new class of potent inhibitors for phospholipase D.”	ic50	0.1250	uM
4-chloro-N-[2-[4-(2-oxo-3H-benzimidazol-1-yl)piperidin-1-yl]ethyl]benzamide	498482: Inhibition of human PLD2 assessed as release of methyl-[3H]choline from choline-methyl-[3H]dipalmitoylphosphatidylcholine after 30 mins by exogenous substrate assay	ic50	0.1300	uM
3,4-difluoro-N-[2-[4-(2-oxo-3H-benzimidazol-1-yl)piperidin-1-yl]ethyl]benzamide	498478: Inhibition of GFP-tagged human PLD2 expressed in human HEK293 cells assessed as decrease in phosphatidylbutanol-[d9] production after 30 mins by mass spectrometric analysis	ic50	0.1300	uM
N-[(2S)-1-(4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decan-8-yl)propan-2-yl]naphthalene-2-carboxamide	349538: Inhibition of GFP-labeled PLD2 in human HEK293 cells	ic50	0.1400	uM
N-[2-[4-(5-fluoro-2-oxo-3H-benzimidazol-1-yl)piperidin-1-yl]ethyl]naphthalene-2-carboxamide	418767: Inhibition of GFP-labelled human PLD2 HEK293 cells	ic50	0.1400	uM
N-[(2S)-1-[(4R)-4-(4-fluorophenyl)-1-oxo-2,8-diazaspiro[4.5]decan-8-yl]propan-2-yl]-1H-indole-2-carboxamide	1532925: Inhibition of GFP-fused PLD2 (unknown origin) expressed in HEK293 cells by cellular assay	ic50	0.1400	uM
1-tert-butyl-3-naphthalen-2-ylpyrazolo[3,4-d]pyrimidin-4-amine	1800492: PLD In Vitro Kinetic Assay from Article 10.1111/cbdd.12319: “1,3-disubstituted-4-aminopyrazolo [3, 4-d] pyrimidines, a new class of potent inhibitors for phospholipase D.”	ic50	0.1500	uM
1-methyl-3-phenylpyrazolo[3,4-d]pyrimidin-4-amine	1800492: PLD In Vitro Kinetic Assay from Article 10.1111/cbdd.12319: “1,3-disubstituted-4-aminopyrazolo [3, 4-d] pyrimidines, a new class of potent inhibitors for phospholipase D.”	ic50	0.1500	uM

CTD chemical–gene interactions

44 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Testosterone	increases expression, affects cotreatment	2
Tetrachlorodibenzodioxin	affects expression, increases expression	2
1-Butanol	decreases reaction, increases activity, affects localization, affects reaction	2
Particulate Matter	increases abundance, increases expression, decreases expression	2
FR900359	affects phosphorylation	1
triphenyl phosphate	affects expression	1
lead acetate	decreases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, decreases expression, increases expression	1
arsenite	affects binding, decreases reaction	1
sodium arsenite	decreases expression	1
cobaltous chloride	decreases reaction, increases expression, increases reaction, increases activity, increases abundance	1
epigallocatechin gallate	decreases reaction, increases expression, increases reaction	1
phosphatidylbutanol	affects reaction, increases abundance, increases reaction	1
Go 6976	increases reaction, decreases reaction, increases expression	1
SB 203580	decreases reaction, increases expression, increases reaction	1
2-(4-nitrophenyl)-4-(4-fluorophenyl)-5-(4-pyridinyl)-1H-imidazole	decreases reaction, increases expression, increases reaction	1
ilimaquinone	decreases reaction, increases activity	1
(N)-methanocarba-2MeSADP	affects reaction, increases phosphorylation	1
jinfukang	affects cotreatment, increases expression	1
Sunitinib	decreases expression	1
Leflunomide	decreases expression	1
Acetylcysteine	increases expression, increases reaction, decreases reaction	1
Air Pollutants	decreases expression, increases abundance	1
Atrazine	increases expression	1
Benzo(a)pyrene	increases expression	1
beta-Endorphin	increases activity	1
Calcitriol	increases expression, affects cotreatment	1
Cholesterol	affects reaction, increases export, decreases reaction	1
Cisplatin	affects cotreatment, increases expression	1
Fentanyl	increases activity	1

ChEMBL screening assays

40 unique, capped per target: 36 binding, 4 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1220056	Binding	Inhibition of PLD2 mediated cancer cell migration in human MDA-231 cells at 200 nM by transwell invasion assay	Design of isoform-selective phospholipase D inhibitors that modulate cancer cell invasiveness. — *Nat Chem Biol*
CHEMBL1794370	Functional	PUBCHEM_BIOASSAY: Cellular PLD2 concentration response. (Class of assay: confirmatory) [Related pubchem assays (depositor defined):AID588854]	PubChem BioAssay data set

Cellosaurus cell lines

6 cell lines: 6 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B2B6	Abcam HeLa PLD2 KO	Cancer cell line	Female
CVCL_F1P6	HyCyte HCT 116 KO-hPLD2	Cancer cell line	Male
CVCL_F5G6	EDITGENE PLD2 Knockout HAP1 Cell Line	Cancer cell line	Male
CVCL_TE44	HAP1 PLD2 (-) 1	Cancer cell line	Male
CVCL_TE45	HAP1 PLD2 (-) 2	Cancer cell line	Male
CVCL_TE46	HAP1 PLD2 (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for PLD2 across ~30M SureChEMBL compounds — explore on Sugi Predict.